Patent GB-478304-A (GB)
Title: Manufacture of indole derivatives
IPC: C07D295/15
Filed: 1936-07-13
Abstract: Aminocarboxylic acids are obtained by reaction of acrylic or methacrylic acid with ammonia, or organic derivatives thereof containing at least one NH2 or NH group, in the presence of water at a raised temperature.  According to the conditions, e.g. the relative proportions of the reagents, ammonia may react with from one to three molecules of the acid, with saturation of the double bond or bonds, while a primary amine may react with one or two molecules of the acid.  The organic ammonia derivatives may be (a) primary or secondary alkyl, hydroxyalkyl, cycloalky or hydroxycycloalkyl amines, such as methyl-, ethyl-, propyl-, butyl-, cyclohexyl-, dodecyl-, stearyl-, oleyl-, monoethanol-, diethanol- or cyclohexyl-amine or abietinylamine; (b) primary or secondary aromatic or aliphaticaromatic amines, such as aniline, phenylenediamine, benzidine, naphthylamines, aminoanthraquinones, benzylamines or phenylethylamine, or (c) heterocyclic compounds containing at least one NH2 or NH group, such as indole and its substitution products, piperidine, carbazole or aminopyridines; amines containing two different groups linked to nitrogen, or amines containing substituents such as halogen atoms, tertiary nitrogen atoms, or nitro, alkoxy, carboxylic, sulphonic or acylamino groups, may also be used.  The reaction may be effected at 40--150 DEG  C. and atmospheric or raised pressure in the presence or absence of an inert solvent or diluent, e.g. an alcohol, a ketone, a hydrocarbon, an inert base or acid, or an ester.  The reaction mixture may include also an acid condensing agent e.g. an inorganic acid such as hydrochloric, boric or phosphoric acid, an acid or acid-reacting salt such as primary sodium phosphate, sodium bisulphate, zinc chloride or aluminium chloride, or an organic acid such as formic, acetic, butyric or chloracetic acid; such acids may be added in the form of salts with the nitrogenous starting materials.  Alternatively, the reaction mixture may include a small proportion of a basic accelerating agent, e.g. an alkali, an alkali phenolate, or a tertiary organic base such as pyridine, quinoline or dimethylaniline. The reaction mixture may include also a substance which prevents polymerization, e.g., an aromatic hydroxy compound such as hydroquinone, or a copper salt. Examples are given in which (1) aniline and acrylic acid yield b -phenylaminopropionic acid; (2) aniline and acrylic acid yield N-di(carboxyethyl)aniline; (3) m-toluidine and acrylic acid yield b -m-tolylaminopropionic acid and N-di(carboxyethyl)-m-toluidine; corresponding products are obtained from xylidines, o-, m- or p-chloraniline, nitranilines, monoacylphenylenediamines, and cresidines; (4) N-hydroxyethyl aniline and acrylic acid yield N-hydroxyethyl-N-carboxy-ethylaniline; (5) ethylaniline and acrylic acid yield N-ethyl-N-carboxyethylaniline; (6) b -naphthylamine and acrylic acid yield b -naphthylaminopropionic acid and N-di(carboxyethyl)-b -naphthylamine; corresponding products are obtainable from a -naphthylamine, aminonaphthols, and naphthylamine- or aminonaphthol-sulphonic or carboxylic acids, while the N-alkyl, N-hydroxyalkyl, N-aryl or N-aralkyl derivatives of these starting materials yield correspondingly substituted naphthylaminopropionic acids; (7) n-butylamine and acrylic acid yield b -butylaminopropionic acid and N-di(carboxyethyl)butylamine; corresponding products are obtainable from methylamine, ethylamine, dodecylamine, octadecylamine and octadecenylamine, while secondary amines such as dimethylamine, diethylamine, dibutylamine, butylethylamine, didodecylamine and dioctadecylamine yield the corresponding N-disubstituted aminopropionic acids; (8) o-phenylenediamine and acrylic acid yield a product of unspecified constitution; (9) cyclohexylamine and acrylic acid yield b -cyclohexylaminopropionic acid; (10) piperidine and acrylic acid yield N-carboxyethylpiperidine; (11) dodecylamine and acrylic acid yield b -dodecylaminopropionic acid and N-di(carboxyethyl) dodecylamine; (12) ammonia and acrylic acid yield tri(carboxyethyl)amine; (13) indole and acrylic acid yield N-(carboxyethyl)-indole; (14) 2-methylindole and acrylic acid yield N-(carboxyethyl)-2-methylindole; (15) p-nitraniline and acrylic acid yield b -p-nitrophenylaminopropionic acid and N-di(carboxyethyl)-p-nitraniline; corresponding products are obtainable from o- or m-nitraniline, 4-nitro-2-aminotoluene, and 6-nitro-2-aminotoluene; (16) N-hydroxyethyl-m-toluidine and acrylic acid yield N-hydroxyethyl-N-carboxyethyl-m-toluidine; (17) ethanolamine and acrylic acid yield b -hydroxyethylaminopropionic acid and N-di(carboxyethyl)ethanolamine; (18) aniline and methacrylic acid yield a -methyl-b -phenylaminopropionic acid; (19) metanilic acid and acrylic acid yield N-di(carboxyethyl)metanilic acid; sulphanilic acid yields a corresponding product; (20) ethylenediamine and acrylic acid yield, according to the conditions, b -aminoethylaminopropionic acid or N : N<1>-tetra(carboxyethyl)ethylenediamine; other polyamines, including polyethylene polyamines, yield corresponding products; (21) o-aminobenzoic acid and acrylic acid yield N-di(carboxyethyl)-o-aminobenzoic acid; (22) 2-hydroxy-5-aminobenzoic acid is converted into its N-di(carboxyethyl) derivative by reaction with acrylic acid; (23) 2-amino-4-hydroxytoluene similarly yields an N-di(carboxyethyl) derivative; (24) p-anisidine and acrylic acid yield b -4-methoxyphenylaminopropionic acid; (25) aminohydroquinone dimethyl ether and acrylic acid yield b -(2 : 5-dimethoxyphenylamino)propionic acid; (26) N-cyanoethyl-m-toluidine and acrylic acid yield N-carboxyethyl-N-cyanoethyl-m-toluidine; (27) N-sulphoethylaniline and acrylic acid yield N-carboxyethyl-N-sulphoethylaniline; (28) phenylglycine and acrylic acid yield N-carboxymethyl-N-carboxyethylaniline; (29) 1 : 2 : 3 : 4-tetrahydroquinoline is converted into its N-carboxyethyl derivative by reaction with acrylic acid; (30) a 7 : 8-hydroxybenzo-3-hydroxy-1 : 2 : 3 : 4-tetrahydroquinoline (obtainable by condensing 1-amino-5-naphthol with epichlorhydrin and heating the product to effect ring-closure) is converted into its N-carboxyethyl derivative by reaction with acrylic acid; 7 : 8-benzo-3-hydroxy-1 : 2 : 3 : 4-tetrahydroquinoline (obtainable by condensing a -naphthylamine with epichlorhydrin and heating the product to effect ring-closure) is similarly converted into an N-carboxyethyl derivative; (31) a mixture of primary amines, obtainable from the acids of palm-kernel oil by the process described in Specification 421,718, is converted into N-carboxyethyl and N-di(carboxyethyl) derivatives by reaction with acrylic acid; oleylamine also yields corresponding products; the products are useful as wetting agents, or as softening agents for artificial silk, or as dispersing agents for calcium soaps; (32) 1 : 4-diaminoanthraquinone and acrylic acid yield N<1>-di(carboxyethyl)-1 : 4-diaminoanthraquinone; other aminoanthraquinones yield analogous products; the anthraquinone derivatives are useful for dyeing acetate artificial silk; in each example, aqueous acrylic acid is used, and a stabilizer, e.g. copper acrylate or copper sulphate, is sometimes added; in example 18, the reaction mixture includes copper sulphate, hydroquinone and red phosphorus.  Specifications 401,435, 465,513, and 466,316 also are referred to.ALSO:A mixture of primary amines, obtainable from the acids of palm-kernel oil by the process described in Specification 421,718, is converted into N-carboxyethyl and N-di(carboxyethyl) derivatives by reaction with acrylic acid. Corresponding products are obtainable similarly from oleylamine.  The products are useful as dispersing-agents for calcium soaps.